Given the high global co-morbidity of HIV and major depressive disorder (MDD), understanding the negative synergistic effects of these two disabling conditions is increasingly important as comprehensive HIV care moves beyond biomedical concerns to include concurrent treatment of mental disorders. Our long-term research program uses perinatal depression (PD) in HIV-infected mothers in southern Brazil as an initial paradigm for intervention studies of the interaction of HIV and MDD. Brazil offers several major advantages for conducting prospective, focused, straight-forward studies of this complex global problem: >98% of pregnant women receive free effective HIV-treatment;mother-to-child HIV transmission rates are <1%;integration of our research program with a large, well-established and successful NICHD-funded program (International Site Development Initiative - NISDI) that seeks to strengthen biomedical research infrastructure for studying HIV-infected women and their newborn children in Latin America;and a highly centralized HIV treatment program for pregnant women, providing access to large numbers of HIV-infected women presenting for care early in their pregnancies. Our R21 application is a segue to an eventual R01 application for a large multi-arm randomized controlled trial of interventions for treatment of PD among women undergoing effective ARV treatment. This present bi-national, multidisciplinary project will enable collection of requisite pilot data on prevalence of PD, identification of risk factors and leverage points for subsequent intervention programs, development of effective strategies for integration of studies of PD into NISDI, and adaptation and validation of screening instruments among the local population. Using the NISDI infrastructure at the Faculty of Medicine, University of Caxias in southern Brazil we will conduct interconnected studies in Porto Alegre (population ~10 million) during the 24-month study period. Study 1: a qualitative study to delineate local concepts of depression, coping strategies, social support, and stigma;and Studies 2 and 3: PD screenings among 450 HIV-infected and 450 control HIV-uninfected women at two time points (during the second trimester of pregnancy and three-four months post-partum) at two large Brazilian Federation hospitals to establish PD prevalence rates and increase understanding of the impact of associated psychosocial factors (frequency of stressful life events, support systems, coping and stigma). We seek to use the high proclivity for seeking prenatal care and newborn health visits that frequently characterizes an often marginalized HIV-infected population of women who may otherwise not be available for study. We hope to use this opportunity to develop effective screening and sustainable PD intervention programs at a time when changes in global and national HIV policies will render such tools of increasing importance to comprehensive care of HIV. PUBLIC HEALTH RELEVANCE: Currently we know little about the nature of depression among HIV-infected women of child-bearing age;particularly in the context of effective HIV treatment programs, which are allowing infected women to live longer and significantly reducing mother-to-child transmission of the virus. This research will begin to address this issue by studying the nature, importance and causes of perinatal depression related to HIV infection and will be used to develop feasible and sustainable options for treating perinatal depression whose efficacy will be tested in a future grant submission.